Insulin resistance is a metabolic dysfunction characterized by inadequate response of insulin target tissues to the physiologic effects of circulating insulin. The principal insulin target organs are skeletal muscle, liver, and adipose tissue. For a healthy person, when blood glucose levels rise during the fed state, the pancreatic beta cells secrete insulin. Insulin facilitates glucose uptake into the skeletal muscle, liver and to a smaller extent the adipose tissue. Simultaneously, insulin blocks the liver from endogenous glucose production (hepatic glucose production) and therefore prevents chronic high blood glucose. The significant portion of this glucose is converted to glycogen by the skeletal muscle and the liver for different purposes. The stored glycogen in the skeletal muscle is easily converted to glucose for immediate energy needs such as walking, running, gardening and other activities before the body switches to using fat for energy.
The liver, on the other hand, is sensitive to blood glucose levels in order to meet the brain’s obligate glucose needs. While other organs prefer to burn fat during the fasting state, the brain is dependent almost exclusively on glucose but has poor storage capability. The liver, therefore, converts stored glycogen to glucose (glycogenolysis) or in an extreme situation, makes glucose from scratch (gluconeogenesis) and releases the glucose into the bloodstream to maintain normal basal glucose levels. Insulin also facilitates the uptake of fat into adipose tissue and prevents the release of stored triglycerides (lipolysis) into the bloodstream. This action of insulin on fats prevents “lipotoxicity” and therefore keeps the liver, muscle, and pancreas sensitive to insulin by preventing excessive fat deposits in the organs.